title: Inhibition of nuclear factor kappa B subunit p65 mRNA accumulation in lipopolysaccharide-stimulated human monocytic cells treated with sodium salicylate.
abstract: Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of inflammatory mediators such as tumor necrosis factor and interleukin-1. The nature of the nuclear factors involved in regulation of these cytokine genes is still unknown. Nuclear factor kappa B (NF-kappa B; heterodimer of p50 and p65) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with lipopolysaccharide. Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation, and a new mechanism of drug action was suggested recently. Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of NF-kappa B activation by preventing the degradation of NF-kappa B inhibitor "I kappa B", blocking the translocation of NF-kappa B into the nuclear compartment. However, the nature of the subunit involved in this mechanism has not been defined. To examine the mechanisms by which salicylates affect cytokine gene transcription, the amount of active and inactive NF-kappa B and NF-kappa B mRNA, in Porphyromonas gingivalis lipopolysaccharide-stimulated human monocytic cells was assessed. High doses of sodium salicylate suppressed NF-kappa B p65 mRNA accumulation, resulting in suppression of total NF-kappa B, p50 on tissue oligonucleotide had no effects on lipopolysaccharide-induced NF-kappa B activation. The data demonstrate that the p65 subunit of NF-kappa B is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of inflammatory mediators.
authors.affiliation: Department of Periodontology and Endodontology, Okayama University Dental School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takashiba
authors.forename: T E
authors.initials: TE
authors.lastname: Van Dyke
authors.forename: S
authors.initials: S
authors.lastname: Amar
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis / Q000037:antagonists & inhibitors; D012980:Sodium Salicylate / Q000494:pharmacology*; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D012980:Sodium Salicylate